Bodily lumen closure apparatus and method

ABSTRACT

An absorbable and expandable closure member used to occlude or exclude a body lumen or cavity, such as a blood vessel, fallopian tube, duct, aneurysmal sac, etc., comprising a closure member comprising one of more sheets of a biomaterial that are rolled, stacked, or folded to form a multilayer construct of a generally cylindrical configuration for deployment through a delivery system, either as a singularly or part of a multiplicity of closure members. The biomaterial is derived from a source material, such as small intestinal submucosa or another remodelable material (e.g., an extracellular matrix) having properties for stimulating ingrowth of adjacent tissue into the biomaterial deployed within the bodily lumen. The closure member is deployed to the bodily lumen from a delivery sheath, cartridge, and/or over a inner guiding member, such as a wire guide or catheter.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority of provisional application Ser. No.60/470,611, filed May 15, 2003, and is a continuation-in-part ofco-pending U.S. patent application Ser. No. 10/206,480, filed Jul. 26,2002, which claims priority to provisional application Ser. No.60/307,893, filed Jul. 26, 2001.

TECHNICAL FIELD

This invention relates to medical devices, more particularly to vesselclosure members, delivery apparatuses, and methods of inserting theclosure members.

BACKGROUND OF THE INVENTION

Open surgical procedures which require incisions through skin, tissue,and organs have a traumatic effect on the body and can lead tosubstantial blood loss. In addition, such procedures expose tissue andorgans to the outside environment which creates an increased risk ofpost-operative infection. After open surgical procedures, patients aregenerally in pain, require substantial recovery time, and aresusceptible to post-operative complications. As a result, open surgicalprocedures are generally higher in cost and have a higher degree ofrisk.

Because of the problems associated with open surgical procedures, theuse of minimally invasive surgical techniques has grown substantiallyover the recent years. As these techniques have developed, the numberand types of treatment devices, including vessel closure members, haveproliferated. Vessel closure members are generally used for sealingfluid passageways in patients, including but not limited to,percutaneous sites in femoral arteries or veins resulting fromintravascular procedures, cardiovascular deformations, fallopian tubesand the vas deferens to prevent conception, and vessels in the brain.Recently, much focus has been placed on developing closure members whichallow quicker hemostasis during intravascular procedures and closuremembers which quickly and effectively occlude fallopian tubes or the vasdeferens to prevent conception.

Intravascular Closure Members

One of the important benefits of minimally invasive intravascularprocedures is less patient blood loss; however, particularly inprocedures in which the femoral artery is accessed, achieving quick andeffective hemostasis at the puncture site still can be problematic. Morerecently, the increased use of heparin and larger sized introducersheaths have presented additional challenges. When larger devices areintroduced into an artery or vein, e.g., 5 Fr or larger, external manualor mechanical compression applied at the entry site, commonly thefemoral artery or vein, has been the standard method of achievinghemostasis, which occurs when a thrombus forms at the vessel opening,thereby preventing further bleeding at the site. External compressiontypically requires that the constant, firm pressure is maintained for upto 30 minutes until hemostasis has been achieved. Even after hemostasis,the site remains vulnerable to further bleeding, especially if thepatient is moved.

To address the obvious inadequacies of using manual or externalcompression alone to close a percutaneous site, a number of devices havebeen developed to assist in closure of the entry site. Various suturingdevices have been developed by Perclose, Inc. and sold by AbbottLaboratories (Redwood City, Calif.) which deliver needles that penetratethe arterial wall to form a knot to close the puncture site. Whilesuturing produces relatively quick and reliable hemostasis when comparedto external compression, it is a technique that requires much skill andexperience on the part of the physician. In addition, the complexity ofthe device has led to reports of failures such as in the ability to forma proper knot and other problems. Another known complication is when thedevice is deployed such that the needles penetrate completely throughthe opposite wall of the target vessel, which can inadvertently lead tothe vessel being closed off, a potentially serious event for thepatient.

Hemostatic collagen plugs offer a lower cost, simpler alternative tosuturing devices and they have increased in popularity, particularly theVASOSEAL® (Datascope Corp., Montvale, N.J.) and ANGIOSEAL™ (The, KendallCo., Mansfield Mass.) closure devices. VASOSEAL® comprises a bovinecollagen sponge plug that is pushed through a blunt tract dilatorthrough the tissue puncture channel where it is deployed against theouter vessel wall to seal the puncture site. The collagen plug swellswith blood and helps occlude blood flow. Manual pressure is stillrequired following initial hemostasis until thrombosis formation issufficient. Complications can occur from the dilator entering the vesselwhere the collagen can be accidentally deployed. Placement of the devicealso requires that the depth of the tissue channel be pre-measured toachieve satisfactory placement. The ANGIOSEAL® device is similar exceptthat it includes a prosthetic anchorplate that is left inside the vesselwhere it biodegrades in about 30 days. Re-puncture at the site cantypically occur at that time at the site, but may be problematic if theanchor device has not been reabsorbed. Additionally both closuredevices, being made of bovine collagen, can cause the formation offibrotic tissue in some patients, which in severe cases, has been knownto be sufficient to restrict blood flow within the vessel. A thirddevice utilizing collagen is the DUETT™ sealing device (VascularSolutions Inc., Minneapolis, Minn.), which comprises a balloon catheterthat delivers a collagen and thrombin solution to the puncture site,which causes fibrinogen formation that seals the puncture site.Generally, collagen plugs have been of limited use in closing largerpunctures sites and are typically intended for procedures involving 5-8Fr introducer sheaths. Even suturing devices are intended for closingpuncture sites in the small to moderate range, although some physicianshave reportedly been able to perform an additional series of steps tosuture larger arterial puncture sites, adding to the time and complexityof the procedure.

Fallopian Tube Closure Members

Currently available methods for permanently occluding or closingfallopian tubes and the vas deferens to prevent conception include tuballigations and vasectomies. Both of these procedures, however, areinvasive, are not generally performed in the doctor's office, and can beexpensive. Prior art methods of occluding the fallopian tubes includeplacing an elastomeric plug or other member in the isthumus or narrowmost portion of the fallopian tubes. These elastomeric plugs or othermembers, however, often migrate in the fallopian tube or otherwisebecome dislodged allowing sperm to pass through the fallopian tube andfertilize an egg released by an ovary. Another prior art fallopian tubeocclusion device is disclosed in Nikolchev et al., U.S. Pat. No.6,176,240 B1. Nikolchev et al. discloses a metallic coil which ispre-shaped into multiple loops separated by straight sections orpre-shaped into a “flower coil.” The metallic coil is inserted into thefallopian tube in an elongated state and when deployed returns to the“flower coil” shape which has a larger diameter than the fallopian tube.The fallopian tube occlusion device of Nikolchev et al. is complicatedrequiring the metallic coil to be pre-formed into a flower shape whichmust have a diameter larger than the interior of the fallopian tube, orthe device will not lodge in the fallopian tube.

What is needed is a simple to use, relatively inexpensive, closuremember that can provide safe and efficient closure of both smaller andlarger vessels, including femoral veins and arteries, fallopian tubes,and the vas deferens. Ideally, such a member should be compatible withother instrumentation used in the procedure, it should be highlybiocompatible, and it should allow subsequent access at the entry siteafter a reasonable period of time without further complications. Inaddition, the closure member should be designed for use with a deliverysystem that allows precise placement without having to pre-measure thetissue channel leading to the vessel, permits the closure member to bereliably placed in the desired location, and delivers the closure membereasily and reliably in the vessel or against the vessel wall.

SUMMARY OF THE INVENTION

The foregoing problems are solved and a technical advance is achieved inan illustrative closure apparatus and delivery system for delivering aclosure member (or ‘construct’), typically an absorbable membercomprising an extracellular matrix material or other bioremodelablematerial, within a body lumen or cavity to substantially restrict orocclude passage of fluids or other bodily materials therethrough orthereinto. In a first embodiment of the invention, the closure apparatuscomprises a construct adapted to function as a hemostatic member. Thehemostatic member typically comprises a generally cylindrical shapeconstruct that is highly expandable In volume when exposed to blood. Inone embodiment, the hemostatic member includes a functional passagewaythat allows the closure member to be mounted over a medical device, suchas a delivery catheter or wire guide, for delivery against a vesselpuncture or into another vascular environment, such as to fill ananeurysm sac, to treat an AV, gastroenteric, or extravascular fistula,treat an arterial or venous malformation, or to occlude a vessel. Asused herein, functional passageway is defined as any longitudinalpathway extending through, or substantially through the hemostaticmember and through which a medical device, such as a catheter or wire,can pass, and which offers little or minimal resistance such that thestructure of the material(s) of construction are not broken, torn, orotherwise disrupted. An example of a non-function pathway would be wherea device is forced through a foam or sponge material where a passagewayis not already substantially preformed such that the cells of the foammust be mechanically separated as the device is forced therethrough.Besides open lumens, examples of functional pathways would includeself-sealing membranes or valves, gel-like or sealant materials, andcompressed, rolled or folded constructs which have natural spacesbetween layers through which a medical device could pass.

In a second aspect of the invention, the hemostatic member includes afirst material, such as a foam material, which is capable of absorbingblood to expand several times (e.g., 6-10×) its diameter to causehemostasis, and a second material, such as a sheet of a biomaterialwhich provides structural integrity (biomaterial being defined herein asany biologically derived material or synthetic matrix material thatincludes growth factors or other biologically active compounds). In oneembodiment used to close arterial or venous punctures made during commonintravascular procedures, the hemostatic member comprises a sheet of anextracellular collagen matrix (ECM), such as small intestinal submucosa(SIS), which is rolled together with a SIS sponge comprising lyophilizedand comminuted SIS that has been formed into a thin layer andcross-linked using one of several known cross-linking agents. It is thehighly-absorbent sponge material that provides most of the radialexpansion of the hemostatic member. The sheet of SIS, when rolled into agenerally cylindrical construct along with the adjacent sheet of spongematerial, adds structural integrity to the construct, allowing it to beused to seal larger puncture channels, such as 9-16 Fr, which typicallyfall outside the capabilities of collagen foam plugs. This is dueprimarily to the fact that the harvested SIS sheet material generallymaintains its structure much longer than the ground collagen or SISsponge when wet. Collagen sponge plugs essentially liquefy when exposedto blood and although then are able to shorten the time of hemostasis inpunctures involving introducers up to 8 Fr in diameter, they are notindicated for sealing larger puncture sites. The two rolled sheets ofSIS are compressed into a cylindrical construct and placed over adelivery catheter. Ideally, the hemostatic member comprises no more thanhalf the length of tissue tract, which typically measures 3-4 cm in anaverage patient. It is within the scope of the invention for hemostaticmember to comprise only the second material, such as a tightly rolledSIS construct, or it could include only the first, foam or sponge-likematerial (e.g., lyophilized SIS). For example, treating lyophilized SISwith more effective cross-linking agents could yield a construct havingincreased structural integrity that is comparable to the illustrativehemostatic member that includes a SIS sheet. SIS and other ECMbiomaterials provide a clinical advantage over biomaterials containingmammalian cells or cellular debris in that they can be processed to beboth highly biocompatible and thus, much better tolerated thantraditional collagen-based implants. SIS is known to have the ability tostimulate angiogenesis and tissue ingrowth to become completelyremodeled as host tissue over time. The process of obtaining purifiedSIS is described in U.S. Pat. No. 6,209,931 to Cook et. al.

The hemostatic member delivery apparatus includes an outer sheathmember, such as an introducer sheath, which may represent the samesheath that is initially used in the intravascular procedure, a pushermember to provide counter force to hold the hemostatic member in placewhile the sheath is being withdrawn, and a wire guide which extendsthrough the lumen of the mounting catheter and provides an atraumaticdistal tip within the vessel. One method of delivering the hemostaticmember to externally seal a puncture site includes the steps of loadingthe hemostatic member subassembly (which also includes the mountingcatheter, wire guide, and pusher member) into the introducer sheathwhile the sheath is within the vessel. A splittable cartridge can beused to temporarily constrain the hemostatic member to facilitate theloading process into the introducer sheath. The hemostatic membersubassembly is configured to correspond to the length of the introducersheath such that when it is fully advanced into the sheath, thehemostatic member is positioned near the distal end of the introducermember. The introducer sheath and hemostatic member subassembly arepartially withdrawn from the vessel such that the blunt end of theintroducer sheath is outside the vessel. The opening narrows as theelastic vessel walls retract after the introducer sheath is withdrawnsuch that re-advancement would cause the introducer sheath to abut theoutside of the vessel or tunica vascularis about the puncture site. Anoptional side hole is located on the delivery catheter just distal tothe distal end to the hemostatic member which can provide a positionalindicator for the delivery subassembly. Blood flowing into the side holeand through the delivery catheter, can be observed by the operator as itflows into a side port catheter, indicating that the tip of theintroducer sheath is still outside the vessel. To make it such thatblood can only enter the lumen of the mounting catheter though the sidehole, a section of the distal portion of the wire guide can be madelarger to act as a seal against the distal end of the mounting catheter.

With the distal tip of the introducer sheath abutting the vessel, thehemostatic member is deployed. A splittable deployment guard placedbetween the hub of the introducer sheath and the pusher member can beused to prevent accidental premature deployment. Once it is removed, theintroducer sheath can be partially withdrawn, while holding the pushermember in position, to expose either a part or all of the hemostaticmember to blood and allow it to expand within the tissue tract. Anoptional second side hole may be formed within the region over which thehemostatic member is mounted. The wire guide can either be advanced toallow blood to flow into the lumen of the mounting catheter, or it canbe withdrawn from the mounting catheter lumen to allow blood to flowthrough the second side hole. Deployment of the hemostatic memberagainst the vessel is accomplished by partial withdrawal of theintroducer sheath, while the pusher member is maintained in position fora few minutes until the hemostatic member has swelled to its fullyexpanded state and has stabilized. The delivery catheter is removed fromthe pathway of the hemostatic member which swells to quickly seal anylumen left by its withdrawal. The pusher member is removed with theintroducer member after stabilization, and external or mechanicalcompression is applied at the site for the recommended period of time oruntil the physician feels it is no longer necessary.

In another aspect of the invention, the distal end of the hemostaticmember includes a plurality of slits, such as two slits dividing thehemostatic member lengthwise into quarters and which extend for about25-30% of its length. Slitting the distal portion of hemostatic memberallows the distal end to expand outward to facilitate the sealingprocess.

In still other aspects of the invention, the second (sheet) material ofthe hemostatic member includes a folded, rather than a rolledconfiguration, which unfolds as the hemostatic member radially expandswithin the tissue channel. The folds can include any number ofconfigurations such as radially-arranged pleat or parallel folds withthe foam sheet typically being interspersed between the folds.

In yet another aspect of the invention, the hemostatic member deliveryapparatus can be adapted to introduce the hemostatic member into ananeurysm to prevent leakage around a stent graft. In one embodiment, thestent graft includes an open section through which an outer deliverycatheter could be introduced that would provide a means to deliver the,hemostatic members to the aneurysm after the stent graft had beenplaced. Afterward, another section of the stent graft would beintroduced through the original stent graft and positioned over the opensection. A second option would be to include a sleeve or other type ofvalve in the graft material through which the delivery system could beintroduced. The valve would then close to prevent leakage of blood. Oneexample of a hemostatic closure member delivery system for treatment ofan aneurysm would comprise a series of hemostatic members placedadjacently over a wire guide and loaded into an outer sheath member,such as an introducer sheath or delivery catheter, typically with theassistance of a pusher member. A second method involves loading one ormore closure members into a loading cartridge which is inserted into thedelivery catheter, whereby a pusher member urges them into thecatheter's passageway for final deployment. In one method of deployment,the pusher member individually deploys the hemostatic member or membersloaded in the catheter. This procedure is repeated with additionalclosure members until the aneurysm is filled. Alternatively, the closuremember(s) can be expelled from the delivery catheter by infusing salineor another fluid via a syringe through a side port in the deliverysystem. This method advantageously pre-hydrates the closure member priorto it reaching the deployment site in the body.

In another aspect of the invention, the hemostatic member and deliverysystem is adapted for delivery into an aneurysm, such as an abdominalaortic aneurysm, such that the delivery catheter is positioned outsideof the graft prosthesis, between the graft and the vessel wall. Thegraft prosthesis is then deployed, leaving the catheter tip inside theexcluded aneurysm. This placement method takes advantage of the factthat the technique is already well known for placement of contrast mediainfusion catheters in this manner. Conveniently, the same catheter forinfusion of contrast can be used for the delivery of the hemostaticmembers. Another advantage is that the graft prosthesis need not bemodified to provide temporary access into the aneurysm so that thecatheter, which would likely be the case if the hemostatic members areto be delivered from the inside of the graft prosthesis.

In yet another aspect of the invention, the closure member constructcomprises a plurality of layers of the second sheet material, such as asingle-layer SIS or another biomaterial, preferably lyophilized, thatare configured to readily separate in the presence of bodily fluid. Theseparating layers create a large amount of surface area to absorb fluidand fill a body lumen or cavity when deployed singularly or as amultiplicity of closure members. SIS or other ECM sheet materialtypically has superior remodeling properties over sponge material, whichis subject to additional processing steps, such as cross-linking andcomminution that may degrade the matrix structure and growth factorstherein and thus, represents a construct that may be more advantageousin clinical situation where rapid swelling is less important than theneed to stimulate remodeling by native tissue within a body lumen, suchas when attempting the exclusion of an aneurysm.

In a first embodiment, the layered sheet closure member is formed byrolling one of more sheets of SIS to form a tightly rolled configurationthat optionally, but not necessarily, includes a functional pathway orlumen extending therethrough. In a second embodiment, the closure memberis created from a stack of individual sheets that are either cut into atubular construct or a squared/rectangular shaped construct that arepreferably unattached to one another or partially laminated such thatthey readily separate when exposed to fluid. In a third embodiment, oneor more sheets of material are rolled around a somewhat rigid orsemi-rigid core member that in one preferred embodiment, comprises twonarrow strips of SIS that are tightly intertwined or braided into anelongate member that is air-dried. The elongate twisted member acts as amandril that facilitates the rolling of the sheet to form the constructand is absorbed or replaced with adjacent tissue along with the sheetlayers following deployment in the body. To facilitate rapid separationof layers of material in each of the above embodiments, a closure membermay include one or more longitudinal splits extending the length of theconstruct. The closure member can be formed by rolling or stackinghydrated ECM sheets, then lyophilizing them, which may result in somedegree of lamination between layers of material. Alternatively, thesheet or sheets may be lyophilized first, then rolled or stack toproduce a looser construct than may facilitate entry of fluid betweenthe layers of material. A less dense ECM material, such as stomachmucosa, can also represent an alternative larger-cell material that whenlyophilized has superior swelling properties similar to sponge material.

In another aspect, provided is a method for closing a passageway in abody of a patient. The method includes providing a closure devicesuitable for delivery to the body passageway, said closure devicecomprising a remodelable collagenous extracellular matrix sheetmaterial, the extracellular matrix sheet material being isolated as asheet material from a collagenous-based tissue source, the remodelablecollagenous extracellular matrix sheet material being rolled or foldedto provide a closure device construct in which the remodelablecollagenous extracellular matrix sheet material spans the entirety ofthe length of the closure device construct and provides extracellularmatrix material extending across the full width of the closure deviceconstruct prior to delivery with adjacent layers of the extracellularmatrix sheet material contacting one another in the construct, theclosure device construct being sized to occlude the passageway and theremodelable collagenous extracellular matrix sheet material beingeffective upon implantation of the closure device construct to providenew tissue growth in the body passageway for filling the passageway withtissue of the patient, wherein the isolated extracellular matrix sheetmaterial has not been subjected to crosslinking. The method alsoincludes inserting the closure device in the passageway.

In another aspect, provided is a method for closing a fallopian tube,vas deferens tube, extravascular fistula or gastroenteric fistula in abody of a patient. The method includes providing a closure devicesuitable for delivery to the body passageway, said closure devicecomprising a remodelable collagenous extracellular matrix sheetmaterial, the extracellular matrix sheet material being isolated as asheet material from a collagenous-based tissue source, the remodelablecollagenous extracellular matrix sheet material being rolled or foldedto provide a closure device construct in which the remodelablecollagenous extracellular matrix sheet material spans the entirety ofthe length of the closure device construct and provides extracellularmatrix material extending across the full width of the closure deviceconstruct prior to delivery with adjacent layers of the extracellularmatrix sheet material contacting one another in the construct, theclosure device construct being sized to occlude the passageway and theremodelable collagenous extracellular matrix sheet material beingeffective upon implantation of the closure device construct to providenew tissue growth in the body passageway for filling the passageway withtissue of the patient. The method also includes inserting the closuredevice in the fallopian tube, vas deferens tube, extravascular fistulaor gastroenteric fistula.

In another aspect, provided is a method for closing a passageway in abody of a patient. The method includes providing a closure device thatincludes an isolated remodelable collagenous extracellular matrix sheetmaterial isolated as a sheet material from a collagenous-based tissuesource, the remodelable collagenous extracellular matrix sheet materialbeing rolled or folded to provide a closure device construct in whichthe remodelable collagenous extracellular matrix sheet material spansthe entirety of the length of the closure device construct and where,prior to delivery, extracellular matrix material extends across the fullwidth of the closure device construct with adjacent layers of theextracellular matrix sheet material situated in the center of theclosure device construct, the remodelable collagenous extracellularmatrix sheet material being effective upon implantation to provide newtissue growth in the body passageway for closing the body passagewaywith tissue of the patient, wherein said adjacent layers of theextracellular matrix sheet material contact one another in the closuredevice construct. The method also includes inserting the closure devicein the body passageway, wherein said inserting is conducted withoutadvancing the closure device over a delivery device, and wherein thebody passageway is a fistula.

In another aspect of the present invention, the closure member is afallopian tube member which after insertion into a fallopian tube,occludes the tube and blocks sperm from contacting a released egg,thereby preventing conception. In one embodiment, the fallopian tubemember includes a loop-shaped metal frame, a first material, aradiopaque binding wire, and a second material, such as a sheet ofbiomaterial, which adds structural integrity. The first material mayinclude, a sponge-like or foam material, which is capable of absorbingblood and fluid, a lyophilized sheet of SIS, or a sheet of air-driedSIS. The second material may be a sheet of SIS.

The fallopian tube member may be formed around a delivery catheter withan outer wall, a distal end, and a lumen extending therethrough. Twoopenings are provided opposite each other in the distal end of thedelivery catheter transverse to the lumen. The metal wire or frame isthreaded through the first opening, the lumen, and exits the secondopening. The metal wire is then formed into a loop-shaped frame.Thereafter, a guide wire catheter with a distal end and a lumenextending therethrough is advanced through the delivery catheter untilthe distal end of the guide wire catheter extends beyond the distal endof the delivery catheter and the loop-shaped metal frame. A firstmaterial, which may be sponge-like, is wrapped around the distal end ofthe guide wire catheter and then a radiopaque binding wire is wrappedaround the loop-shaped frame and the first material. In one embodiment,a second sheet of material is then wrapped around the loop-shaped frame,the first material, and the radiopaque binding wire. The ends of theloop-shaped frame are then trimmed flush with the outer wall of thedelivery catheter. The frame, as defined herein, may assume amultiplicity of configurations and may comprise more than one component.The primary function of the frame is to have a portion thereof be ableto engage the walls of the vessel to anchor the fallopian tube membertherein and/or to cause trauma to the walls to encourage migration offibrocytes into the member material to encourage tissue ingrowth thatallows the fallopian tube member to become a permanent occlusion toprevent the passage of gametes (eggs or sperm) or other material.

One method of delivering the fallopian tube member into a fallopian tubeincludes the steps of providing a uterine introducer catheter which isinserted transcervically through a uterus to the ostium. The deliverycatheter and coaxial guide wire catheter with fallopian tube memberformed thereon are then advanced through the uterine introducercatheter. Once the fallopian tube member is positioned, the guide wirecatheter is withdrawn. As the guide wire catheter is withdrawn, thefallopian tube member is deployed. The delivery catheter and introducercatheter are then removed.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 depicts a pictorial view of an illustrative embodiment of thepresent invention;

FIGS. 2-3 depict steps in the formation of the hemostatic member of FIG.1;

FIG. 4 depicts a partially sectioned view of the hemostatic deliverysubassembly, including the hemostatic member of FIG. 1 prior to beingloaded into an introducer sheath;

FIG. 5 depicts a partially sectioned view of the hemostatic memberdelivery apparatus;

FIGS. 6-7 depict the device being deployed at a vessel puncture site;

FIG. 8 depicts a pictorial view of a hemostatic member having distallongitudinal slits;

FIGS. 9-9A depict the embodiment of FIG. 8 following deployment;

FIGS. 10-12 depict views of embodiments of hemostatic members comprisingfolded material;

FIG. 13 depicts an embodiment of the hemostatic member comprising only afirst material;

FIGS. 14-15 depict an embodiment of the present invention beingintroduced through a stent graft to treat an aneurysm;

FIG. 16 depicts a partially sectioned view of the delivery of FIGS.14-15;

FIGS. 17-19 depict an alternative delivery apparatus and method forfilling an aneurysm around a stent graft prosthesis;

FIG. 20 depicts a side view of the apparatus of FIGS. 17-19;

FIG. 21 depicts a partial cross-section of the of the fallopian tubemember of the present invention;

FIGS. 22-29 depict steps in the formation of the fallopian tube memberdepicted in FIG. 21;

FIGS. 30-31 depict the fallopian tube member shown in FIG. 21 beingdeployed into a fallopian tube;

FIGS. 32-33 depict perspective views of an embodiment of the closuremember comprising rolled sheet material in a configuration that is splitlongitudinally, prior to and following deployment;

FIGS. 34-36 depict embodiments of a closure member comprising a stack ofsheets of material;

FIG. 37 depicts a view of a closure member being formed by wrapping asheet of material around a braided core member of same;

FIG. 38 depicts a perspective view of the formed closure member of FIG.37;

FIG. 39 depicts a top view of the core member of FIG. 37 being formed;

FIGS. 40-41 depict methods of loading the embodiment of FIG. 32 into aloading cartridge; and

FIG. 42 depicts the embodiment of FIG. 32 being formed within theloading cartridge using the method of FIG. 41.

DETAILED DESCRIPTION

In one embodiment of the present invention, depicted in FIGS. 1-16, theclosure member is a hemostatic member 11 which is delivered to atreatment site within the body of a patient to provide an externalhemostatic seal or intravascular occlusion to prevent blood flow, suchas from a blood vessel 48 punctured during a procedure using anintroducer sheath 27 to gain access of a patient's artery or vein, or tofill an aneurysm 58, especially where a stent graft 57 has been placed.The hemostatic member 11 comprises a construct that is able to absorbblood and swell in diameter, yet has sufficient structural integrity inits expanded state to exert a gentle expansile force that provides amore effective seal for achieving hemostasis than collagenous foamalone, particularly in larger puncture channels (above 8 Fr). Theillustrative hemostatic member 11, depicted in FIG. 1, includes a rolledconfiguration 17 comprising a layer 18 of two materials formed byrolling together a first, sponge or foam-like material 12 capable ofgreatly expanding in diameter as it absorbs blood, and a second,non-sponge material 13 comprising a sheet of a biomaterial, such assmall intestinal submucosa (SIS) or another extracellular matrix (ECM).Other possibilities include pericardium, liver basement membrane, orother membranes or sheets harvested or derived from collagenous-basedtissue. Possible first materials include lyophilized SIS sponge or otherECM materials, non-extracellular collagen sponge (such as bovine-derivedcollagen), or synthetic hemostatic materials such as GELFOAM® (PharmaciaCorporation, Peapack, N.J.). In the illustrative embodiment, the firstmaterial 12 includes a small square (e.g., 2-3 cm) of SURGISIS™Soft-Tissue Graft (SIS) (Cook Biotech, Inc., West Lafayette, Ind.) whilethe second material includes a similar-sized sheet of sponge comprisinglyophilized and cross-linked SIS, typically about 1 mm in thickness.Animal studies suggest that the illustrative hemostatic member 11 can beused to effectively seal vessel punctures made by introducer sheathshaving an O.D. up to 16 Fr. While naturally derived biomaterials,particularly bioremodelable materials like SIS, are generally preferred,synthetic materials, including those into which growth factors are addedto make them bioremodelable, are also within the scope of thisinvention.

FIG. 2 depicts the formation of the rolled hemostatic member 11 of FIG.1, whereby the lyophilized SIS sheet 12 is laid upon the non-lyophilizedSIS sheet 13, which typically has been pre-wetted. The two materials12,13 form a single layer 18 which is rolled around a rolling aid 20,such as a section of 0.010″ stainless steel wire, to form a constructthat assumes a tightly-compressed state 21 in which it will remain untildeployment. After the hemostatic member 11 has been rolled into thecompressed state 21, a binding or constraining means 24, such as a pieceof elastic suture, is wrapped around the hemostatic member for a fewminutes or hours until the compression has been stabilized and theconstruct will remain in that state. The binding means 24, which couldalso include any wrapping or compressive mechanism, such as a press, isthen removed. The rolling aid 20 is also removed, creating a functionalpassageway 14 within the hemostatic member 11 that allows it to beloaded over a catheter or wire guide as will be discussed later. Afterremoval of the rolling aid 20, the ends of the rolled construct aretruncated along a pair of cut lines 25 to create the first and secondends 15,16 of the hemostatic member. The illustrative hemostatic member11 is capable of expanding to 6-10× its original volume (typically abouttwice its diameter) in the presence of blood, the majority of thatexpansion contributed by expansion of the first, sponge material 12.While the SIS sheet 12 of the first material is capable of swelling aswell, e.g., from 100μ to 200μ, its primary function is to providestructural integrity that allows the hemostatic member 11 to radiallyexpand in a controlled manner, such as by unrolling or unfolding, whilebeing able to exert a gentle force or pressure against tissue to providea useful degree of ‘bite’ or fixation. In a traditional foam collagenplug, the collagen swells until it contacts adjacent tissue, but theblood-soaked plug at that point, does not have a sufficient constitutionto press outward against the walls of the tissue tract in any clinicallymeaningful way, particularly in larger tissue channels (i.e., above 8Fr). The SIS sheet 13, which comprises an intact section of tissue thatis harvested from porcine intestine, sterilized, and processed to removethe muscular layers and cellular debris, has superior linear strengthcompared to a sheet of processed collagen, and the added structuralintegrity provides additional clinical utility over a typical collagenplug or a hemostatic member comprising SIS foam alone. Therefore, theillustrative hemostatic member 11 of FIG. 1 obtains a clinical benefitfrom the combination of the separate functions of the two materials12,13. One skilled in the art should recognize that the highlyabsorptive sponge or foam material 12 could be augmented in a number ofother ways to achieve some degree of the desired performancecharacteristics, besides the bi-layer sheet configuration, depicted. Forexample, the second material 13 could include strips or particles ofsome other biomaterial or suitable synthetic material more durable thanfoam that while lacking the absorptive capabilities of the sponge 12,would add increased structural integrity during expansion.

FIGS. 4-5 depict an exemplary hemostatic member delivery apparatus 26configured for placement of the hemostatic member 11 against the outsideof a vessel to seal a puncture. The illustrative hemostatic memberdelivery apparatus 26 includes a hemostatic member delivery subassembly65, depicted in FIG. 4, and a standard or modified introducer sheath 27(e.g., a 6 cm COOK CHECK-FLO® Introducer Sheath (Large Valve, Assembly)(Cook Incorporated), shown in FIG. 5 with a portion of the deliverysubassembly 65, which can comprise the standard vascular introducersheath which has already been introduced during the procedure, or asecond introducer sheath, sized for use with the delivery subassembly,to replace the original sheath, which would be exchanged over theoriginal wire guide used in the procedure. Referring to FIG. 4, thehemostatic member delivery subassembly 65 includes the hemostatic member11 which is placed over a delivery catheter 29, such as a standard 3-4Fr polyethylene or polytetrafluoroethylene catheter. A wire guide 32 isdisposed within the passage 36 of the delivery catheter 29 to assist inre-cannulation of the vessel. The illustrative wire guide 32 comprises adistal floppy or atraumatic portion 33, such as a COOK MICROPUNCTURE™wire guide (Cook Incorporated) followed by a larger diameter portion 34,such as a standard 0.038″ wire guide, which can be soldered over thefloppy portion 33. Typically, the two portions 33,34 measure about 2-3cm in length, with about a third of that being the floppy portion. Theremainder of the wire guide 32 comprises a mandril wire 66, such as a0.014-0.018″ stainless steel wire, which is attached to the two coiledportions 33,34 and extending proximally where it can be manipulated bythe operator.

The larger-diameter portion 34 of the wire guide 32 serves to provide aseal of the passage 36 of the delivery catheter 29 when it abuts thecatheter's distal end 35, allowing the operator to control whether bloodcan flow into the passage 36. This can allow the delivery catheter 29 toinclude positional monitoring capabilities to indicate whether thehemostatic member 11 is in the vessel, or properly positioned outsidethe vessel. To accomplish this, a side hole 37 is positioned just distalthe first end 15 of the hemostatic member 11 which allows blood in thevessel to communicate with the passage 36, which is otherwise sealed bythe wire guide 32. It may also be used for the injection of contrastmedia or dye. If the operator detects blood flowing from a side portcatheter 39 (FIG. 5) that communicates with the passage 36 of thedelivery catheter 29, then the side hole 37 and probably, at least aportion of the hemostatic member 11 are both still located within thevessel. However, when blood no longer can be observed flowing from thepassage 36 to the side port 39, it is an indication that side hole 37and hemostatic member 11 are outside of the vessel wall where deploymentshould occur. A second side hole 38 may be positioned along the deliverycatheter 29, typically about 5 mm within the hemostatic member 11, toallow blood to flow to the lumen 14 of the hemostatic member 11, whichcan lead to more rapid expansion following deployment.

Another component of the hemostatic member delivery subassembly is apusher member 28 which is disposed over the delivery catheter 29 to abutthe hemostatic member 11. The function of the pusher member 28 is toprovide a counter force sufficient to hold the hemostatic member 11 inposition against the vessel during deployment and the initial stagesfollowing hemostasis. The illustrative pusher member typically has adiameter of 6-12 Fr, depending on the size of the hemostatic member 11and the accompanying introducer sheath, and can be made of a variety ofpolymers, such a polyurethane, polyethylene, etc. that yield good columnstrength while preferably, having some degree of lateral flexibility.

The illustrative hemostatic member subassembly includes one component, aloading cartridge 40, which is not part of the hemostatic memberdelivery apparatus 26 in its final, pre-deployment state. The loadingcartridge, which in the example of FIG. 4 includes a section ofsplittable PTFE sheath (such as the PEEL-AWAY® Introducer Sheath (CookIncorporated), is configured such that it can facilitate the loadingprocess of the hemostatic member 11 into the proximal end 67 of theintroducer sheath 27 by providing a hard, protective sheath or conduitthat is easier to push through the proximal opening of the introducersheath 27. The delivery subassembly 65 is inserted into the opening atthe proximal end 67 until the cartridge 40 contacts the proximal end,then the cartridge 40 is peeled back (split apart) as the hemostaticmember 11 is inserted into the introducer sheath 27, after which it isdiscarded.

FIG. 5 depicts the hemostatic member delivery apparatus 26 assembled fordeployment with the hemostatic member 11 loaded into the introducermember 27. The pusher member 28 includes a proximal hub 30 which engagesand locks with the proximal hub 31 of the delivery catheter 29 so thatthe two components can be introduced together into the introducer sheath27. An optional deployment guard 42 is positioned between the introducersheath 27 and hub 30 of the pusher member 28 and sized so that when thedelivery subassembly 65 is fully advanced into the introducer sheath 27,the distal end 15 of the hemostatic member 11 is generally aligned withthe distal end 50 of the introducer sheath 27, which is the properpre-deployment position. The illustrative deployment guard 42 is about 2cm in length, allowing for full exposure of the hemostatic member 11,which typically is about 1.5 cm in length. In the illustrativeembodiment, the delivery catheter 29 extends about 3-4 cm beyond the endof the pusher member 28 and about 2 cm beyond the distal end 50 of theintroducer sheath 27 after it has been loaded therein. To deploy thehemostatic member 11 so that it is allowed to fully expand with absorbedblood within the tissue channel, the deployment guard 42 is peeled awayand removed such that the introducer sheath 27 can be withdrawn relativeto the delivery subassembly 65, which is maintained in place by theoperator.

The basic procedure for delivering the hemostatic member 11 against theoutside wall of the vessel 48 is shown in FIGS. 6-7. Typically, theprocedure to access the vessel will initially involve percutaneous entryof the vessel using a hollow needle, followed by introduction of a wireguide, then a dilator over the wire guide, and ultimately, anintravascular introducer sheath 27, the latter typically to provide aconduit for introducing another medical device, such as a catheter,retrieval device, etc. Once the procedure is completed and the ancillaryinstrumentation removed, either the original wire guide is removed,leaving the introducer sheath 27 ready to accept the hemostatic deliverysubassembly 65, or the original introducer sheath is removed over thewire guide and a new introducer sheath 27, which is packaged as part ofthe hemostatic member delivery apparatus 26, is exchanged over theexisting wire guide. The original wire guide is then removed and thedelivery subassembly 65 is introduced through the new introducer sheath27. In FIG. 6, the distal end 50 of the introducer sheath 27 is situatedwithin the vessel 48 with the delivery subassembly 65 already havingbeen loaded therein such that the delivery catheter 29 and new wireguide 32 extend from the introducer sheath 27 into the vessel lumen 49.Referring also to FIG. 5 now, the hub 30 of the pusher member 28 and thehub 31 of the delivery catheter 29 are locked together at this point (inFIG. 6), and the deployment guard 42 is in place between the introducersheath 27 and hub 30 (not shown in FIG. 6) to properly align thehemostatic member 11 within the introducer sheath 27 for deployment. Thehemostatic member 11, fully inside the introducer sheath 27 at thispoint, is at least partially within the vessel, and therefore, ispartially exposed to blood at its distal end. Additionally, the firstside hole 37 is situated within the vessel at this point, indicating tothe operator by the presence of blood through the side port 39 (shown inFIG. 5) that the delivery apparatus 26 needs to be withdrawn from thevessel before deployment can occur. The entire hemostatic memberdelivery apparatus 26 is partially withdrawn until the distal tip 50 isoutside the vessel wall 51 and tunica vascularis 55 surrounding thevessel 48 as shown in FIG. 7. The distal portions of the deliverycatheter 29 and the wire guide 32 remain in the vessel lumen 49. Becausethe tissues of the vessel wall 51 and tunica vascularis 55 are somewhatelastic, the puncture hole 47 created in the vessel 48 begins tocontract as soon as the blunt-tipped introducer sheath 27 is withdrawn,such that when the introducer sheath 27 is subsequently re-advancedtoward the vessel 48, using gently forward pressure, the tip 50 abutsthe vessel wall 51 and does not re-enter the vessel lumen 49. Thisadvantageously positions the distal end 15 of the hemostatic member 11against the vessel wall 49 for deployment. Furthermore, the presence ofthe delivery catheter 29 and wire guide 32 through the puncture hole 47helps to center the hemostatic member 11 over the puncture hole 47during deployment, which involves removing the deployment guard 42 andwithdrawing the introducer sheath 27 while maintaining the deliverysubassembly 65 in place, thereby fully exposing the hemostatic member 11to blood exiting the puncture hole 47. At deployment, the wire guide 32either can be advanced to open the passage 36 of the delivery catheter29 such that blood can flow to the pathway or lumen 14 of the hemostaticmember 11 via the second side hole 37, or both the delivery catheter 29and wire guide 32 can be withdrawn, thereby hastening the absorption ofblood via the hemostatic member lumen 14. In either case, the deliverycatheter 29 and wire guide 32 must be removed before full deploymentoccurs. At deployment, the illustrative hemostatic member 11 unfolds asthe foam material rapidly swells with blood, closing the lumen 14 leftby the withdrawn delivery catheter 29. As shown in FIGS. 9 and 9A, thehemostatic member quickly assumes the expanded (wet) state 22 and fillsthe tissue channel 46, thereby sealing the puncture site 47. For thefirst few minutes after deployment (e.g., 4-5), the pusher member 28 ismaintained in position to provide a counter force while the hemostaticmember 11 is fully expanding. Afterward, the pusher member 28 is removedfrom the tissue channel 46, as shown in FIG. 9A, and external pressureor mechanical compression is typically applied over the site until theformation of thrombus results in the stabilization of hemostasis. Thetime required for external compression varies according to the patient'sblood chemistry, anticoagulant treatment, and the size of the puncturehole 47.

FIGS. 8-9 depict a hemostatic member 11 that includes a modificationintended to facilitate more rapid and complete sealing of the areasurrounding the puncture site 47. As shown in FIG. 8, the distal 25-30%portion about the first end 15 of the hemostatic member 11 includes apair of slits 53, extending therethrough and located 90° with respect toone another such that four longitudinal sections 54 or quadrants areformed. It would also within the scope of the invention for the slits 53to extend only partially through the width hemostatic member 11. In thepresence of blood, these sections 54 function to spread laterallyoutward, as depicted in FIG. 9, to more quickly provide a broad surfacecontact the outer vessel wall 51 and tunica vascularis 55 and quicklyseal the puncture site 47. The remaining, uncut portion toward thesecond end 16 functions to provide the structural integrity to thehemostatic member 11. During deployment of the embodiment of FIGS. 8-9,the introducer sheath 27 may be withdrawn only to expose the portionhaving the slits 53, before eventually exposing the entire hemostaticmember 11 to blood (FIG. 9A). While the illustrative embodiment includesa pair of slits 53, a single slit 53 or more than two slits 53 may alsoprovide a clinical benefit over a solid, uncut hemostatic member 11.Additionally, the slits 53 can comprise a lesser or greater portion ofthe length of the hemostatic member 11 compared to the illustrativeembodiment.

While a hemostatic member 11 comprising the rolled configuration 17depicted in FIGS. 1 and 8 is well-adapted for rapid and effective radialexpansion, there are other numerous configurations of hemostatic members11 that would be included within the present invention. FIGS. 10-12depict end views of hemostatic members 11 that comprise a foldedconfiguration 56. Expansion occurs when the hemostatic member 11 swellswith blood, forcing the layers 18 to unfold, thereby increasing itsvolume. The embodiment of FIG. 10 includes a series of folds 70comprising layers 18 of the two materials 12,13 arranged in a star-likeconfiguration with the foam material 12 on the outside and the adjacentSIS sheet 13 positioned underneath for structural support. In theillustrative embodiment the functional pathway 14 comprises a third,sealant material 68, such as a gel material having hemostaticproperties, such as GELFOAM®. The gel does not interfere with thehemostatic member 11 being loaded over a catheter or wire guide, and canbe added beforehand or afterward. Another additive to this particularembodiment is a thrombotic agent 69, such as thrombin, powder, placedbetween the folded layers 70. When blood contacts the thrombin, itcauses the formation of fibrinogen, which further speeds hemostasis.Inclusion of such a thrombotic agent 69 would have utility in virtuallyany embodiment encompassed by the present invention. FIG. 11 depicts ahemostatic member 11 loaded in an introducer sheath 27 where thehemostatic member 11 comprises a series of parallel folds 70 of thefirst and second materials 12,13. A catheter or wire guide (not shown)could be introduced through adjacent layers 18 in the center of theconstruct to form a functional pathway 14 with the layers 18 thenconforming around the device. A third embodiment having a foldedconfiguration 56 is depicted in FIG. 12, whereby the folds 70 arearranged in an overlapping pinwheel configuration. The sponge material12 is located inside of the sheet material 13 in the illustrativeembodiment; however, this arrangement can be reversed as it could in anyof the other embodiments. In the illustrative embodiment of FIG. 12, afunctional pathway 14 is formed between the inside edges of the folds70.

The inclusion of a functional pathway 14 that advantageously permits thehemostatic member 11 to be loaded over a delivery device, such as acatheter or wire guide, for delivery into or against the vessel is oneaspect of the invention that can provide more precise and efficientdelivery. Hemostatic devices, such as the embodiment of FIG. 13 whichmay lack the other aspects of the invention, could be configured toinclude a functional pathway 14 for delivery in the manner depicted inFIGS. 6, 7, and 9 or other delivery strategies that involve thehemostatic device being delivered over a catheter and/or wire. It shouldbe noted that although the embodiment of FIG. 13 includes only thefirst, foam or sponge material 12, a hemostatic member 11 comprisingonly an SIS sponge 12 it is possible to provide a sponge with addedstructural integrity, depending on the cross-linking agent used, suchthat the sponge can be compressed more than it typically could otherwiseto have greater expandability and be possibly slower to break apart orliquefy in the presence of blood.

In a second use of the hemostatic member 11 of the present invention,the hemostatic member delivery system 26 invention can be modified todeliver the hemostatic member through or around a stent or stent graft,such as graft to treat an abdominal aortic aneurysm (AAA), particularlyto cause hemostasis within the aneurysm to help prevent an endoleak suchas around the stent graft, through a collateral vessel and back throughthe artery, through a hole in the graft material, or because the graftmaterial is too porous. In one embodiment depicted in FIG. 14, thehemostatic members 11 are delivered through a modified bifurcated stentgraft 57 that includes open section 61 in the stent frame 60 that lacksthe covering material 59 that covers the remainder of the stent. Thehemostatic member delivery apparatus 26 includes an outer deliverycatheter 64, typically made of a flexible polymer, for navigatingthrough the open section 61 and into the aneurysm 58 where a series ofhemostatic members 11 are delivered to fill the space and achievehemostasis. After the hemostatic members 11 are deployed, theinterventional radiologist can introduce a second section of stent graft(not shown) to close the open section 61. A second option of introducinga hemostatic member 11 through a stent graft 57 into an aneurysm isdepicted in FIG. 15, wherein the flexible delivery catheter 64 isintroduced through a valve 62, such as a sleeve of the graft material59, which forms the opening 61 in the stent graft 57. Such a valve orsleeve could comprise many possible configurations that temporarilypermit access to the aneurysm, but any blood leaking back through thevalve 62 when closed, if any, would not be clinically important. Oneskilled in the art should be able to conceive of additional ways toadapt a stent graft so that it could permit introduction of a hemostaticmember into the adjacent aneurysm.

In one embodiment of the hemostatic member delivery apparatus 26,depicted in FIG. 16, for achieving hemostasis or pre-emptive hemostasisin an aneurysm or other large space, the hemostatic members 11 areloaded sequentially over a wire guide 32 that extends through the lumen45 of the pusher member 28 and through outer delivery catheter 64. Thepusher member 28 is advanced to urge the hemostatic members 11 from theouter delivery catheter 64, or it is maintained in position while theouter delivery catheter 64 is withdrawn, thereby deploying thedistal-most hemostatic member 11. The delivery apparatus 26 of FIG. 16is merely exemplary and could easily be modified, especially forintravascular delivery to other sites, such as AV fistulas, vesselmalformations, or to occlude a vessel.

FIGS. 17-19 depict another method and apparatus 10 for delivery aplurality of hemostatic members 63 into an aneurysm 58 in which thedelivery catheter or member 64 is situated outside of the graftprosthesis 57 prior to the deployment thereof, obviating the need forrequiring access through the graft prosthesis in order to deliverhemostatic members into the aneurysm. In the illustrative method, acatheter, typically one adapted for flushing or infusing the aneurysmwith contrast media, is navigated through an iliac artery and placedwith the tip 86 is located with the aneurysm to be excluded by a graftprosthesis 57, such as the illustrative ZENITH® AAA Endovascular Graft(FIG. 17). This procedure is typically already part of the overallprocedure so that the physician can image the aneurysmal sacunderfluoroscopy. In the example procedure depicted, the graftprosthesis delivery catheter 80 is then introduced and graft prosthesis57 deployed such that the catheter lies outside the stent graftprosthesis 57, such as shown in FIG. 18, where it is positioned betweenthe leg 87 of the prosthesis and the walls of the iliac artery 81 withthe tip 86 and distal portion of the catheter 64 still residing withinthe aneurysm 58. As shown in FIG. 19, a plurality of hemostatic members63 is then deployed into the aneurysm from the catheter 64 until thedesired amount of filling is achieved (usually that required to ensureremodeling of the entire aneursymal sac). Depending on the size of thehemostatic member 11 and aneurysm 58 to be treated, 30 or morehemostatic members 11 may be required to fill the aneurysm sufficientlyto prevent endoleaks, particularly of the Type II kind, by blocking ordisrupting the inflowing and outflowing collateral vessels which supplythe sac with blood. The hemostatic members are deployed by urging themone at a time from the delivery catheter using a well-known means suchas a pressurized fluid, (e.g., saline) or a pusher mechanism, such asthat shown in FIGS. 15-16.

FIG. 20 depicts an apparatus that uses saline, water, or another fluidto urge the hemostatic member 11 from the delivery catheter 64. Theillustrative apparatus includes a delivery catheter, such as a 7-8 FrFLEXOR® Sheath (Cook Incorporated), with a proximal hub 82 configured toaccept a sheath or other device at the proximal end, and furtherincluding a side port 84 with an connector 90 for connecting to ainfusion supply source 85, such as the illustrative syringe, which isable to infuse a sufficient amount of infusate (generally about 10 cc)to hydrate a single hemostatic member 11, which in the illustrativeembodiment, is about 2 cc in volume. In the illustrative embodiment, thehemostatic member 11 is loaded into a cartridge 83 that is sized to beinserted into the proximal hub 82 and passageway 89 of the deliverycatheter 64. The cartridge 83 may be sized to accommodate more than onehemostatic member 11. A well-known type of pusher mechanism 28 is usedto urge the hemostatic member 11 into the cartridge and then further oninto the passageway 89 of the delivery catheter 64, beyond the pointwhere the side port 84 feeds into the catheter 64. The stopcock 91 onthe connector 90 is then opened and the infusate is delivered from thesyringe 85, thereby urging the hemostatic member through and out of thecatheter 64. Additional hemostatic members are loaded and delivered inthe same manner until the aneurysm sac is filled.

It may be advantageous to deploy hemostatic members 11 of differentsizes when excluding the aneurysm. For example, a shorter hemostaticmember 11, e.g., 10-20 mm, may be initially deployed to embolize thecollateral vessels, i.e., the lumbar and inferior mesenteric arteries,that can continue to pressurize the sac. Longer hemostatic members,e.g., 25-60 mm, are then deployed into the sac which contribute themajority of the total aneurysm-filling material. Laboratory studiesusing sheep demonstrated that embolization of the entire aneursymal sacimmediately after placement of the graft prosthesis using SIS closuremember, advantageously led to a completely organized thrombolitic sacocclusion and elimination of future endoleaks in a significant number ofstudy animals.

FIGS. 32-39 depict a series of closure or hemostatic member 11embodiments that are particularly well adapted for aneurysm exclusion inthat rather than including a sponge material to facilitate rapid andmaximum expansion of the construct, the closure member comprisesmultiple layers of one or more sheets of the second, sheet material 13,such as lyophilized SIS, that are configured to separate upon contactwith bodily fluid and swell to help occlude or exclude a body passagewayor other space, such as an aneurysmal sac. In the treatment ofaneurysms, it is preferred that the material selected is one thatadvantageously remodels into native tissue, such as connective (e.g.,fibrinous) tissue, to permanently exclude the aneurysm, rather thanmerely being absorbed by the body over time, which could leave theaneurysmal sac still vulnerable to rupture.

FIG. 32 depicts an embodiment of a closure member 11 comprising a singlesheet 12 of a remodelable material, such as SIS or another ECM material,that is formed into a rolled configuration 17. The sheet 11 or closuremember 11 is preferably, but not essentially, lyophilized prior to orafter being formed into the rolled configuration 17. If the construct islyophilized after being formed into the rolled configuration 17,hydrated SIS/ECM sheets are used. The closure member 11 is then splitlongitudinally with the longitudinal split 87 defining a firstlongitudinal portion 88 and a second longitudinal portion 89 that areheld together prior to deployment by an outer constraint, such as aloading cartridge 83 and/or the delivery catheter 64 (FIGS. 17-19). Thelongitudinal split 87 allows the two longitudinal portions 88,89 toreadily unroll and separate from one another (FIG. 33), thereby creatingadditional spaces 91 between the layers 90, which results in the bodilyfluid quickly coming in contact with additional surface area. Typically,separable layers causes the closure member to swell more rapidly andmore fully than it would otherwise. Optionally, the longitudinalportions 88,89 can be reattached after being split with a weak adhesive,dissolvable threads, or another temporary attachment means that permitsseparation of the portions in the presence of fluid. A closure member 11that is split into more than two longitudinal portions is alsocontemplated. While an intact (unsplit) closure member of a rolled(single sheet) configuration is certainly within the scope of thepresent invention, the fluid must infiltrate the construct from theoutside and the layers are not configured to quickly separate from oneanother.

One method of loading a split closure member 11 into a cartridge 83, isdepicted in FIG. 40. Rather than making the longitudinal split 87completely through the length of the closure member 11, a short uncutsection 98, e.g., 5% of total length, remains at about the second end 15of the construct. A pulling mechanism 99, such as the illustrative wireor thread, is looped through the longitudinal split 87 and over theuncut section 98 or fed through a hole 101 made therethrough (FIG. 41).In both embodiments, the wire 99 is fed through the passageway 100 atthe first end 102 of the loading cartridge 83 and out of the second end103 thereof so that the closure member can be pulled into the cartridgevia the wire or thread. As shown if FIG. 42, the closure member 11 ispulled through until the short uncut section 98 is exposed, along withat least a small portion of the longitudinal split 87. The uncut section98 is then cut off or otherwise removed such that the (new) second end15 of the closure member 11 is flush with the second end 103 of thecartridge 83, thereby producing a closure member in which thelongitudinal split 87 traverses the entire length of the construct. Thesplit closure member 11 is then pushed into a delivery catheter 64, suchas a 8 Fr. FLEXOR® sheath, from which it is deployed into the patientusing a technique already described, such at that for the method ofdeploying the apparatus depicted in FIG. 20.

FIGS. 34-36 depicts embodiments of the present invention in which thesheets 12 of SIS or ECM material are stacked to form a multiplicity oflayers 90 that are not laminated to one another, thereby permittingseparation in the present of bodily fluid following deployment. Theembodiment of FIG. 34 comprises a cylindrical or tubular shaped stack 96of sheets 12 that is formed by either coring a square or irregular stackof sheets, such as shown in FIG. 34, with an appropriate cutting tool ortrimming a stack of sheets into a cylindrical shape. The square-shapedstack 97 depicted in FIG. 34 can be loaded into the round passageway ofa cartridge or delivery system such that it assumes more of a rounded,generally cylindrical cross-sectional profile, such as shown in FIG. 36.The alternative embodiment of FIG. 36 further includes an outer wraplayer 92 enclosing the multiplicity of layers 90. To facilitate quickseparation and migration of fluid into the spaces between the layers 90,the outer wrap layer 92 can remain unattached to itself such that itunrolls more easily to expose the spaces 91 between the layers 90within, or it can be made such that it readily disintegrates orfractures to fulfill the same purpose. The number of layers 90 (sheets)used to form the illustrative closure member 12 depends on the size ofthe construct, which is usually determined by the ID of the deliverycatheter, the biomaterial used (e.g., stomach submucosa is thicker thanSIS) and whether the material is lyophilized before or after it isassembled into the stacked configuration 97. Generally, the closuremember 11 used to fill an aneurysm comprises about 20-30 stacked sheets12, depending on final diameter desired. Alternatively, the layers 90can be formed by a series of alternating folds of a single sheet (orseveral sheets), rather than stacking multiple sheets; however, thefolds would at least partially block fluid flow into the interlayerspaces and may add additional bulk to the construct, without anaccompanying improvement in function.

FIGS. 37-38 depict an closure member 11 which further includes a coremember 93 at the center of a rolled configuration 17 of a sheet 12 ofSIS or other ECM material. As depicted in FIG. 37, the core member 93acts as a mandril around which the sheet 12 is wrapped to form theconstruct, thus greatly facilitating the process. Preferably, but notnecessarily, the core member comprises a biomaterial that is eitherabsorbed or remodeled by body tissue and which is either the same as ordifferent from that comprising the sheet 12. The illustrative coremember 93 comprises a pair of thin, hydrated strips 94,95 of SIS (e.g.,each 2 mm in width) that are intertwined into a single twisted orbraided member. To add rigidity that advantageously assists in therolling process, the core member is air dried after formation. Thisoptional step results in a semi-rigid member 93 that has much lesspliability and absorptive ability than the sheet material 12 thatsurrounds it. If made of SIS or an ECM, the core member 93 may beremodeled into tissue, although it is not essential that it do so, noris it important that it typically does not contribute significantly tothe absorption of blood or other bodily fluid.

Another embodiment of the closure member 11 of the present invention,depicted in FIGS. 21-31, includes a fallopian tube member which isinserted in the patient's fallopian tube transcervically through theuterus. Tissue in the fallopian tube then grows around the closuremember and occludes the fallopian tube. Sperm is blocked from reachingeggs that are released from the ovaries thereby preventing conception.The illustrative fallopian tube member 192 of the present invention asshown in FIG. 21 includes a rolled configuration having a frame 170,such as the illustrative loop-shaped frame ending in barbs 189 and 191,a first layer of material 184, preferably including a biomaterial suchas an ECM, a binding wire 186 which also serves as radiopaque marker,and an optional second material 188 comprising a sheet of biomaterial.It should be noted, however, that the fallopian tube member canbasically comprise any of the construct embodiments disclosed hereinwith respect to the configuration of the sheets (rolled vs. folder,stacked, etc.) and the composition of layers (sheet vs. sheet+sponge,etc.).

FIGS. 22-29 depict the formation of the rolled fallopian tube member. Adelivery catheter 150 having an outer wall 152, a proximal end 154 end,a distal end 156, and a lumen 158 extending through the length of thecatheter is provided. The delivery catheter may range in size, and in apreferred embodiment 5 Fr. Two openings 160 and 162 are formed oppositeone another in the distal end 156 of the delivery catheter transverse tothe lumen 158. A wire 164 is threaded through opening 160, through thelumen 158 and exits the delivery catheter at opening 162. The wire issufficiently long that the ends 166 and 168 of the wire extend beyondthe outer wall 152 of the delivery catheter 150. The wire 164 may beformed from copper, stainless steel, or other suitable biocompatiblemetals or metal alloys. The wire 164 may be a round wire having adiameter from about 0.001 to 0.006 inches. In one embodiment, the roundwire is about 0.005 inches in diameter. Alternatively, the wire may be aflat wire and have a thickness of about 0.0001 to 0.0005 inches. In oneembodiment, the thickness of the flat wire is about 0.0005 inches.

A loop-shaped frame 170 is formed at the distal end of the deliverycatheter by pulling the wire 164 through the distal end 156 of thedelivery catheter 150 as shown in FIG. 23. Alternatively, the wire maybe pre-formed into the loop-shaped frame and each end of the loopthreaded through one of the openings in the delivery catheter 150.Another alternative loop-shaped frame 170 is depicted in FIG. 24 whereinthe wire 164 crosses over itself to form the loop. A guide wire catheter174 depicted in FIG. 25 having a distal end 176 and a proximal end 178is placed in the delivery catheter such that the distal end 176 of theguide wire catheter extends past the distal end 156 of the deliverycatheter 150. The guide wire catheter 174 is slidably disposed in thedelivery catheter and further has a lumen 180 for accepting a guide wire182 to aid in the placement of the closure member. Like the deliverycatheter, the guide wire catheter also may vary in size, and in oneembodiment is a 3 or 4 Fr catheter.

As shown in FIG. 26, a piece of compressed sponge-like material or foamis 184 wrapped around the distal end 176 of the wire guide catheter 174.Alternatively, a single sheet of lyophilized SIS or air dried SIS may bewrapped around the distal end 176 of the guide wire catheter. In anotherembodiment a tube shaped piece of SIS may be slid over the distal end176 of the guide wire catheter to cover the end of the catheter. Thecompressed SIS sponge or tube may or may not be wrapped around theloop-shaped metal frame 170. In one embodiment, the sponge-like material184 is compressed SIS as previously discussed with respect to thehemostatic member. In the presence of blood or other fluid, thecompressed SIS sponge 184 expands about 2-3× its original diameter wheninserted into the fallopian tube and occludes a section of the fallopiantube. Subsequently, a wire 186 is wrapped around the sponge-likematerial 184 and the loop-shaped frame 170 as shown in FIG. 27. Thehelical wire 186 compresses the sponge and assists in keeping the spongein place. In addition, the helical wire 186 serves as a marker which canbe seen via conventional visualization methods such as x-ray orultrasound in order to assist in placement of the fallopian tube member.In one embodiment the metal wire 186 is platinum. However, those skilledin the art will realize that other biocompatible metals or metal alloyssuch as stainless steel, nitinol, etc., may also be used. A thin sheetof material 188 is then wrapped around the loop-shaped frame 170, thesponge-like material 184, and the helical metal wire 186 in order tosecure the construct together as shown in FIG. 28. In one embodiment,the sheet of material 188 is SIS which will expand slightly aspreviously discussed with respect to the hemostatic member and assist inoccluding the fallopian tube by encouraging ingrowth of native cells. Abinding or constraining means, such as the elastic suture or compressivemechanism shown in FIG. 3 and previously discussed with respect to thehemostatic member, is wrapped around the construct until the compressionof the construct has been stabilized and the member remains in thecompressed state. The binding means is then removed. The ends 166 and168 of the loop-shaped frame 170 are then cut off at the outside wall152 of the delivery catheter 152 to form barbs 189 and 191 (as shown inFIG. 29). The closure member 192 is ready for deployment as shown inFIG. 29. When the member 192 is deployed in a fallopian tube, thetruncated ends 189 and 191 of the loop-shaped frame 170 (originally ends166 and 168) act as barbs and lodge into the wall of the fallopian tubein order to prevent migration of the member 192 in the tube. The traumacaused to the vessel walls also stimulate ingrowth of native cells intothe material 184,188, which in the case of ECM materials, allowsremodeling or replacement of the ECM with native tissues over time.

While the fallopian tube member 192 may be formed around a guide wirecatheter as previously described, it will be appreciated by those ofordinary skill in the art that the fallopian tube member may be formedaround a rolling member as described above with respect to thehemostatic member, and then placed over the guide wire catheter prior toinsertion of the member.

FIGS. 30-31 depict one exemplary delivery apparatus for placement of thefallopian tube member 192 in a fallopian tube in order to seal orocclude the tube. The delivery apparatus in its simplest form is thedelivery catheter 150 and the guide wire catheter 174. The basicprocedure for delivering the fallopian tube member is shown in FIG. 30.A uterine introducer catheter 194 is inserted transcervically through auterus 196 to the ostium 198. The delivery catheter 150 with innercoaxial guide wire catheter 174 and fallopian tube member 192 areadvanced through the introducer catheter 194 into the fallopian tube200. The wire marker 186 (not shown) provides good radiopacity and aidsin the exact positioning of the fallopian tube member 192 in the tube200. Once the fallopian tube member is positioned, the guide wirecatheter 174 is withdrawn as depicted in FIG. 31. As the guide wirecatheter is retracted, a proximal end 202 of the fallopian tube member192 contacts the distal end 156 of delivery catheter 150 preventing thefallopian tube member from being withdrawn into the delivery catheter.The fallopian tube member 192 has now been deployed over the guide wireand the delivery catheter 150 and introducer catheter are removed 194.On deployment, the sponge-like material 184 and to some extent the sheetmaterial 188 of the fallopian tube member 192 expand thereby occludingthe fallopian tube 200. As previously discussed the ends 166 and 168 ofthe loop-shaped frame 170 of the fallopian tube member 192 lodge in thewalls 204 of the fallopian tube and prevent the member 192 frommigrating. Thereafter, the sheet of material 188 fuses into the tissueof the fallopian tube 200 and causes the fallopian tube tissue to growand occlude the tube.

One skilled in the art will realize that the fallopian tube member maybe deployed in the fallopian tube by numerous other methods well knownin the art. For example, the fallopian tube member 192 may be loadedinside a delivery catheter and deployed in the fallopian tube by pushingthe member out of the delivery catheter with the coaxial guide wirecatheter. Alternatively, the fallopian tube member may be deployed usingfiberoptic scope or hysteroscope.

The advantages of the fallopian tube closure device of the presentinvention are numerous. Because the fallopian tube member of the presentinvention may be positioned without surgery, the patient is less likelyto suffer substantial blood loss or post-operative infection. Moreoveras no incisions are made the patient experiences less pain and recoversfrom the procedure more quickly than other surgical sterilizationprocedures. Finally, the fallopian tube members of the present inventioncan be inserted in a doctor's office under local anesthetic. As aresult, the use of the fallopian tube member of the present inventionprovides a less costly option for sterilization than procedures whichrequire hospitalization.

Illustrative embodiments of the present invention have been described inconsiderable detail for the purpose of disclosing a practical, operativestructure whereby the invention may be practiced advantageously. Thedesigns described herein are intended to be exemplary only. The novelcharacteristics of the invention may be incorporated in other structuralforms without departing from the spirit and scope of the invention. Theinvention encompasses embodiments both comprising and consisting of theelements described with reference to the illustrative embodiments.Unless otherwise indicated, all ordinary words and terms used hereinshall take their customary meaning as defined in The New Shorter OxfordEnglish Dictionary, 1993 edition. All technical terms shall take ontheir customary meaning as established by the appropriate technicaldiscipline utilized by those normally skilled in that particular artarea. All medical terms shall take their meaning as defined by Stedman'sMedical Dictionary, 27^(th) edition.

What is claimed is:
 1. A method for closing a passageway in a body of apatient, comprising: providing a closure device suitable for delivery tothe body passageway, said closure device comprising a remodelablecollagenous extracellular matrix sheet material, the extracellularmatrix sheet material being isolated as a sheet material from acollagenous-based tissue source, the remodelable collagenousextracellular matrix sheet material being rolled or folded to provide aclosure device construct in which the remodelable collagenousextracellular matrix sheet material spans the entirety of the length ofthe closure device construct and provides extracellular matrix materialextending across the full width of the closure device construct prior todelivery with adjacent layers of the extracellular matrix sheet materialcontacting one another in the construct, the closure device constructbeing sized to occlude the passageway and the remodelable collagenousextracellular matrix sheet material being effective upon implantation ofthe closure device construct to provide new tissue growth in the bodypassageway for filling the passageway with tissue of the patient,wherein the isolated extracellular matrix sheet material has not beensubjected to crosslinking; and inserting the closure device in thepassageway.
 2. The method of claim 1, wherein said inserting comprisesdelivering the closure device into the body passageway in a deliverysheath lumen.
 3. The method of claim 1, wherein said inserting comprisesdelivering the closure device into the body passageway over a guidewire.
 4. The method of claim 1, wherein the extracellular matrix sheetmaterial is effective to stimulate angiogenesis in the patient.
 5. Themethod of claim 1, wherein the closure device consists essentially ofthe extracellular matrix sheet material.
 6. The method of claim 1,wherein the extracellular matrix sheet material comprises submucosaltissue.
 7. The method of claim 1, wherein the construct includesmultiple layers of the extracellular matrix sheet material providing agenerally cylindrical configuration.
 8. The method of claim 2, whereinthe body passageway is a fallopian tube, vas deferens tube orgastroenteric fistula.
 9. The method of claim 8, wherein the closuredevice includes a rolled amount of the extracellular matrix sheetmaterial providing a generally cylindrical shape.
 10. The method ofclaim 1, wherein the extracellular matrix sheet material comprisessubmucosal tissue.
 11. The method of claim 1, wherein the constructincludes multiple layers of the extracellular matrix sheet materialproviding a generally cylindrical configuration.
 12. The method of claim1, wherein the bodily passageway is a fallopian tube.
 13. The method ofclaim 1, wherein the bodily passageway is a vas deferens tube.
 14. Themethod of claim 1, wherein the bodily passageway is an extravascularfistula.
 15. The method of claim 1, wherein the bodily passageway is avascular vessel.
 16. The method of claim 1, wherein the adjacent layersof the extracellular matrix sheet material are substantiallyuninterrupted across the width of the closure device construct.
 17. Themethod of claim 16, wherein the remodelable collagenous extracellularmatrix sheet material is rolled to provide the device construct, andwherein the device construct is formed by rolling and compressing theremodelable collagenous extracellular matrix sheet material.
 18. Themethod of claim 1, wherein the remodelable collagenous extracellularmatrix sheet material is rolled to provide the device construct, andwherein the remodelable collagenous extracellular matrix sheet materialis stabilized in a compressed and generally cylindrical rolledconfiguration.
 19. The method of claim 18, wherein the remodelablecollagenous extracellular matrix sheet material is pre-wetted.
 20. Themethod of claim 1, wherein the remodelable collagenous extracellularmatrix sheet material is lyophilized.
 21. The method of claim 1, whereinthe remodelable collagenous extracellular matrix sheet material isfolded to provide the closure device construct.
 22. A method for closinga fallopian tube, vas deferens tube, extravascular fistula orgastroenteric fistula in a body of a patient, comprising: providing aclosure device suitable for delivery to the body passageway, saidclosure device comprising a remodelable collagenous extracellular matrixsheet material, the extracellular matrix sheet material being isolatedas a sheet material from a collagenous-based tissue source, theremodelable collagenous extracellular matrix sheet material being rolledor folded to provide a closure device construct in which the remodelablecollagenous extracellular matrix sheet material spans the entirety ofthe length of the closure device construct and provides extracellularmatrix material extending across the full width of the closure deviceconstruct prior to delivery with adjacent layers of the extracellularmatrix sheet material contacting one another in the construct, theclosure device construct being sized to occlude the passageway and theremodelable collagenous extracellular matrix sheet material beingeffective upon implantation of the closure device construct to providenew tissue growth in the body passageway for filling the passageway withtissue of the patient; and inserting the closure device in the fallopiantube, vas deferens tube, extravascular fistula or gastroenteric fistula.23. A method for closing a passageway in a body of a patient,comprising: providing a closure device that includes an isolatedremodelable collagenous extracellular matrix sheet material isolated asa sheet material from a collagenous-based tissue source, the remodelablecollagenous extracellular matrix sheet material being rolled or foldedto provide a closure device construct in which the remodelablecollagenous extracellular matrix sheet material spans the entirety ofthe length of the closure device construct and where, prior to delivery,extracellular matrix material extends across the full width of theclosure device construct with adjacent layers of the extracellularmatrix sheet material situated in the center of the closure deviceconstruct, the remodelable collagenous extracellular matrix sheetmaterial being effective upon implantation to provide new tissue growthin the body passageway for closing the body passageway with tissue ofthe patient, wherein said adjacent layers of the extracellular matrixsheet material contact one another in the closure device construct; andinserting the closure device in the body passageway so as to close thebody passageway, wherein said inserting is conducted without advancingthe closure device over a delivery device, wherein the closure device issized and configured to close the body passageway without folding theclosure device upon itself, and wherein the body passageway is afistula.
 24. The method of claim 23, wherein said adjacent layers of theextracellular matrix sheet material contact one another in the closuredevice construct.
 25. The method of claim 24, wherein the adjacentlayers of the extracellular matrix sheet material are substantiallyuninterrupted across the width of the closure device construct.
 26. Themethod of claim 23, wherein the closure device construct comprises agenerally cylindrical construct.
 27. The method of claim 23, with theremodelable collagenous extracellular matrix sheet material being rolledto provide the closure device construct.